Pyrazolopyridine carboxamide derivative and phosphodiesterase (pde) inhibitor containing the same

Abstract

A novel pyrazolopyridine carboxamide derivative is provided that is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine carboxamide derivative is represented by the following general formula (1): (Example: 2-ethyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide).

1 . A pyrazolopyridin-4-ylcarboxamide derivative represented by the general formula (1): 
     
       
         
         
             
             
         
       
     
     [wherein R′ is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms (optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, and a halogen atom), an alkoxy group having 1 to 6 carbon atoms, an alkylsulfanyl group having 1 to 6 carbon atoms, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 6 carbon atoms, or an amino group optionally substituted with an alkyl group having 1 to 6 carbon atoms, R 2  is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms (optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an alkoxy group having 1 to 6 carbon atoms, and a halogen atom), a cycloalkyl group having 3 to 8 carbon atoms, an alkanoyl group having 1 to 6 carbon atoms, a carboxyl group, an oxime group, or a cyano group, R 3  is a hydrogen atom, a halogen atom, or a hydroxyl group, and R 4  is a pyridyl group optionally substituted with a halogen atom, an N-oxide thereof, or a phenyl group optionally substituted with a halogen atom] or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       2 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 3  is a hydrogen atom. 
   
   
       3 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 1  is an alkoxy group having 1 to 6 carbon atoms or a hydroxyalkyl group having 1 to 6 carbon atoms. 
   
   
       4 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 2  is a cycloalkyl group having 3 to 6 carbon atoms, a cyano group, or an optionally substituted alkyl group having 1 to 4 carbon atoms (being optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom). 
   
   
       5 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound represented by the general formula (1) is
 2-ethyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   2-isopropyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   2-isopropyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloro-1-oxypyridin-4-yl)amide,   2-cyclopropyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   2-cyclopropyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloro-1-oxypyridin-4-yl)amide,   7-methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   2-difluoromethyl-7-methoxy-pyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   7-methoxy-2-methoxymethylpyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   2-cyano-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide,   7-hydroxymethyl-2-trifluoromethylpyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide, or   7-(1-hydroxyethyl)-2-trifluoromethylpyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide.   
   
   
       6 . A phosphodiesterase (PDE) inhibitor comprising the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       7 . A pharmaceutical comprising as an active ingredient the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 1 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       8 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 2 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 1  is an alkoxy group having 1 to 6 carbon atoms or a hydroxyalkyl group having 1 to 6 carbon atoms. 
   
   
       9 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 2 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 2  is a cycloalkyl group having 3 to 6 carbon atoms, a cyano group, or an optionally substituted alkyl group having 1 to 4 carbon atoms (being optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom). 
   
   
       10 . The pyrazolopyridin-4-ylcarboxamide derivative according to  claim 3 , or a pharmaceutically acceptable salt or hydrate thereof, wherein, in the general formula (1), R 2  is a cycloalkyl group having 3 to 6 carbon atoms, a cyano group, or an optionally substituted alkyl group having 1 to 4 carbon atoms (being optionally substituted with one or more substituents selected from the group consisting of a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, and a halogen atom). 
   
   
       11 . A phosphodiesterase (PDE) inhibitor comprising the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 2 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       12 . A phosphodiesterase (PDE) inhibitor comprising the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 3 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       13 . A phosphodiesterase (PDE) inhibitor comprising the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 4 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       14 . A phosphodiesterase (PDE) inhibitor comprising the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 5 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       15 . A pharmaceutical comprising as an active ingredient the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 2 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       16 . A pharmaceutical comprising as an active ingredient the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 3 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       17 . A pharmaceutical comprising as an active ingredient the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 4 , or a pharmaceutically acceptable salt or hydrate thereof. 
   
   
       18 . A pharmaceutical comprising as an active ingredient the pyrazolopyridin-4-ylcarboxamide derivative according to  claim 5 , or a pharmaceutically acceptable salt or hydrate thereof.